PROJECT ABSTRACT This application requests MSTP funding for the Penn State MD/PhD Program. Our program has a 20-year history of training outstanding students and providing them with the tools and experiences needed to become successful physician-scientists and leaders in academic medicine. Penn State has a talented and interactive faculty committed to biomedical research and MD/PhD career development. The students enrolled in our MD/PhD program are fully supported by the Dean of the College of Medicine during the medical school years and by faculty grants and individual fellowships during the graduate phase of the program. An MSTP award would leverage this institutional commitment, allowing us to increase the program from our current level of 6 students admitted per year to 8 students admitted per year. Over the past 10 years, Penn State has substantially improved the quality of the MD/PhD program through several targeted investments: (i) full autonomy of the MD/PhD program to select and admit qualified students; (ii) ~100% increase in institutional support, from less than $1 million to nearly $2 million per year; (iii) recruitment of >70 physician-scientist faculty members, including several departmental chairs and program directors, plus a recent initiative to recruit an additional 5-10 new physician-scientist faculty members; (iv) a 45% increase in the applicant pool size; (v) an increase in the number of matriculating students from 33 to 51; (vi) a doubling of the number of matriculated underrepresented minority students; and (vii) establishment of closer ties with our sister campus at University Park (UP) through the development of joint programs with Engineering Sciences & Mechanics and Molecular & Cellular Integrated Biosciences, as well as the appointment of an Associate Director of the MD/PhD program on the UP campus. The curriculum for the MD/PhD program is interdisciplinary and integrated. Students are exposed to both clinical and basic scientific activities longitudinally throughout their training, thus emphasizing the need to integrate biomedical research with patient care. MD/PhD-specific programmatic activities include a monthly seminar series where students present their own research and learn from visiting speakers; a bimonthly Clinical Research Conference where students learn to use clinical problems as a springboard for investigating the basic and translational sciences literature; a longitudinal Clinical Exposure Program, in which students hone their clinical skills by selecting a clinical preceptor and attending clinic at least one half day per month while pursuing their research; an annual retreat held on the UP campus; and several courses and seminars that specifically deal with translational biomedical research and MD/PhD career development. Most importantly, Program leaders use a very hands-on approach with our students. We take mentorship extremely seriously and we invest a significant amount of time meeting with and listening to our students to make their training experience at Penn State one that will not only be rigorous, but also provide a training path that fosters their career development, enabling them to excel in their future careers as physician-scientists.